This project investigates the roles of autonomic nervous system (ANS activity. attention. and information processing and their interrelationships in the pathology, etiology, and prognosis of psychiatric disorders and studies their underlying biological and psychological processes. ANS activity is assessed by peripheral measures such as skin conductance. heart rate. and skin temperature. Subjects are tested under conditions of rest, presentation of tones, and performance on various tasks, especially reaction time tests of attention. Biological mechanisms are investigated by correlating these variables with enzyme activity, neuropeptides, and levels of biogenic amines and their metabolites and with brain dysfunction as revealed by CT, MRI, and PET scans. Recent and current work: 1) In schizophrenic patients we found that the atypical neuroleptic clozapine markedly attenuates ANS activity compared to a typical neuroleptic and placebo. Clozapine did not improve reaction time but there was evidence that it increased the efficiency of information processing, and this was mediated by a reduction of hallucinations. 2) Several methods to study respiratory sinus arrhythmia. an index of parasympathetic (vagal, cholinergic) control of heart rate have been developed and compared. Different methods are highly correlated, reliable, and resistant to direct effects of body movements. 3) Adolescents with Childhood Schizophrenia are being tested on the same protocol used with children with various other diagnoses. They show excessive resting ANS activity but lower than normal ANS activity during a task, low responsivity to novel and meaningful stimuli, and slow habituation. These results are similar to our previous findings in adult schizophrenics and quite distinct from those seen in other types of child and adult psychopathology. 4) Subjects with closed head injuries and with focal brain lesions are being tested on the same protocols used with the schizophrenics in part to explore the neurobiology of schizophrenia and in part to study central determinants of ANS reactions.